Microscale Interrogation of 3D Tissue Mechanics.

Jian Zhang,Cynthia A Reinhart-King,Neil C Chada

doi:10.3389/fbioe.2019.00412

Jian Zhang, Cynthia A Reinhart-King + Show 1 more

Open Access

https://doi.org/10.3389/fbioe.2019.00412

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Abstract

Cells in vivo live in a complex microenvironment composed of the extracellular matrix (ECM) and other cells. Growing evidence suggests that the mechanical interaction between the cells and their microenvironment is of critical importance to their behaviors under both normal and diseased conditions, such as migration, differentiation, and proliferation. The study of tissue mechanics in the past two decades, including the assessment of both mechanical properties and mechanical stresses of the extracellular microenvironment, has greatly enriched our knowledge about how cells interact with their mechanical environment. Tissue mechanical properties are often heterogeneous and sometimes anisotropic, which makes them difficult to obtain from macroscale bulk measurements. Mechanical stresses were first measured for cells cultured on two-dimensional (2D) surfaces with well-defined mechanical properties. While 2D measurements are relatively straightforward and efficient, and they have provided us with valuable knowledge on cell-ECM interactions, that knowledge may not be directly applicable to in vivo systems. Hence, the measurement of tissue stresses in a more physiologically relevant three-dimensional (3D) environment is required. In this mini review, we will summarize and discuss recent developments in using optical, magnetic, genetic, and mechanical approaches to interrogate 3D tissue stresses and mechanical properties at the microscale.

Highlights

Tissues are composed of a large collection of extracellular matrix (ECM) macromolecules (Frantz et al, 2010) and various types of cells (Figure 1A)
The direction of molecular tension can be detected when combined with fluorescence polarization microscopy (Brockman et al, 2018). These synthetic tension probes can be applied to virtually any surface including stiff glass that is not suitable for Traction Force Microscopy (TFM), and have potential applications in 3D systems when functionalized to ECM fibers or incorporated into elastic microbeads as discussed earlier (Neubauer et al, 2019)
The resolution of micro-elastography is limited to tens of microns, as compared to the optical diffraction limit reached by Brillouin microscopy (Scarcelli et al, 2015; Kennedy et al, 2017)

Summary

INTRODUCTION

Tissues are composed of a large collection of ECM macromolecules (Frantz et al, 2010) and various types of cells (Figure 1A). Tissues and native ECMs are heterogeneous, anisotropic (Jones et al, 2015), and undergo constant non-linear local remodeling through strain stiffening, stress relaxation (Nam et al, 2016; Han et al, 2018), matrix degradation, and matrix deposition (Wolf et al, 2007; Attieh et al, 2017). Such features can only be revealed through microscale, but not bulk, mechanical characterization.

Limitations

CONCLUSIONS AND OUTLOOK